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Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02731729
Recruitment Status : Active, not recruiting
First Posted : April 7, 2016
Last Update Posted : December 10, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Brief Summary:
The purpose of this research study is to learn whether patients whose disease grows after being treated with nivolumab or pembrolizumab respond to ipilimumab (Yervoy®) alone or in combination with nivolumab (Opdivo®).

Condition or disease Intervention/treatment Phase
Melanoma Drug: ipilimumab Drug: nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 2 Study of Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy
Study Start Date : April 2016
Actual Primary Completion Date : July 1, 2018
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: ipilimumab and nivolumab
For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes.
Drug: ipilimumab
Other Name: Yervoy

Drug: nivolumab
Other Name: Opdivo

Experimental: ipilimumab
In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses.
Drug: ipilimumab
Other Name: Yervoy




Primary Outcome Measures :
  1. objective response as defined by RECIST v1.1 criteria [ Time Frame: week 18 ]
    as defined by RECIST v1.1 criteria by week 18.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. AJCC (2009) Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Patients with a history of uveal melanoma are not eligible.
  2. Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with computerized tomography (CT) scan. Patients must have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) and a separate lesion amenable to biopsy.
  3. Histologic proof of melanoma reviewed and confirmed by the enrolling site.
  4. Previous treatment with a PD-1 or PD-L1 inhibitor with documented progression of disease on most recent CT scan. Progression of disease is defined as 1) the appearance of a new measureable lesion (>10 mm) on cross-sectional imaging or physical examination OR 2) enlargement of previously detected lesions on two consecutive imaging studies OR 3) enlargement of a previously detected lesion with correlative symptomatology on one cross-sectional imaging study. Patients remain eligible if they had a previous response to a PD-1 inhibitor, including patients who had a complete response, partial response or stable disease (SD). Primary progressing patients are defined as those who received anti-PD-1 therapy within 2 months of study enrollment. Patients with relapsed disease are defined as those who received their last dose of PD-1 blocking antibody ≥2 months prior to enrollment.
  5. Patients who received adjuvant PD-1 therapy who then develop measurable disease are eligible. However, they must have received their last dose of PD-1/PD-L1 blockade within two months of enrollment in this study. They will be stratified with patients who have primary progressive disease.
  6. Life expectancy of greater than 3 months.
  7. Age ≥ 18 years old.
  8. Eastern Cooperative Oncology Group performance status = 0 or 1 or Karnofsky Performance Status equivalent.
  9. Patients must have adequate organ and marrow function as defined below:

    1. White blood cells >2, 000/mcL
    2. Absolute neutrophil count >1,500/mcL
    3. Platelets >100,000/mcL
    4. Hemoglobin > 9.0 g/dL
    5. Total bilirubin ≤ 1.5 X institution's upper limit of normal
    6. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X institution's upper limit of normal for patients with no concurrent liver metastases, OR ≤ 5 X institution's upper limit of normal for patients with concurrent liver metastases
    7. Serum creatinine < 1.5x OR creatinine clearance of at least 40
  10. Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the start of study drug. A woman of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 50 in the absence of other biologic or physiologic causes.
  11. Women with child bearing potential and men with reproductive potential must be willing to practice acceptable methods of contraception.
  12. Ability to understand and the willingness to sign a written informed consent document.
  13. Willingness to undergo biopsy of metastatic site or site of unresectable disease prior to randomization.

Main Exclusion Criteria:

  1. History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible. Consult the study Medical Monitor if unsure whether second malignancies meet the requirements specified above.
  2. Any major surgical procedures or external beam radiotherapy within 14 days prior to study drug administration.
  3. Use of other investigational drugs within 28 days prior to study drug administration.
  4. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month and require treatment with less than 10mg/day prednisone equivalent for at least 2 weeks prior to study drug administration.
  5. Prior exposure to either ipilimumab or combined checkpoint blockade.
  6. Any diagnosis of autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, adrenal insufficiency on replacement dose steroids, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  7. Pregnant women and lactating women.
  8. History of uveal melanoma.
  9. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV or HCV infection, which will be allowed). Once‑documented negative result for HIV, HBV, and HCV is sufficient.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and psychiatric illness/social situations that would limit compliance with study requirements.
  11. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted.
  12. Patients with history of any grade 4 toxicity during previous anti PD-1 treatment or history of Grade 3 or higher pneumonitis.
  13. Patients with a history of Grade ≥2 neuropathy.
  14. Prisoners or patients who are involuntarily incarcerated.
  15. Children under the age of 18.
  16. Patients who require hemodialysis.
  17. Patients with a history of allergy to study drug components or history of a severe hypersensitivity reaction to any monoclonal antibody.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02731729


Locations
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United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94134
United States, New Jersey
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
United States, New York
Memorial Sloan Kettering Westchester
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18103
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Parker Institute for Cancer Immunotherapy
Bristol-Myers Squibb
Investigators
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Study Director: Ramy Ibrahim, MD Parker Institute for Cancer Immunotherapy

Additional Information:
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Responsible Party: Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier: NCT02731729     History of Changes
Other Study ID Numbers: PICI0001
16-043 ( Other Identifier: Memorial Sloan Kettering Cancer Center )
First Posted: April 7, 2016    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018

Keywords provided by Parker Institute for Cancer Immunotherapy:
Ipilimumab
Nivolumab
Stage III-IV Melanoma
Progressed or Relapsed on PD-1 Inhibitor Therapy
16-043

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents